BACKGROUND AND OBJECTIVES: In mantle cell lymphoma (MCL), abnormalities additional to t(11;14) including those affecting genes involved in the p53 pathway, are important for disease development and progression. This study aimed to assess the frequency, relationship and impact of p53 abnormalities and those of its inhibitor mdm2 in blastoid and non-blastoid MCL in leukemic phase. DESIGN AND METHODS: Isolated blood lymphocytes from 21 patients with MCL in leukemic phase, characterized by the presence of t(11;14), were analyzed by flow cytometry and by fluorescent in situ hybridization in order to investigate whether there is a correlation between overexpression and deletion of p53, overexpression of mdm2 and gain of chromosome 12. Results were also correlated with morphologic subtypes, proliferative activity assessed by expression of Ki67 and clinical outcome. RESULTS: Cells from 2/21 (10%) and 7/21 (33%) patients overexpressed p53 and mdm2, respectively. No single case expressed both proteins. Ten out of 19 (53%) patients had a hemizygous loss of 17p (p53) including the 2 patients (11%) overexpressing p53. Gains of chromosome 12 (mdm2) were found in only 2 cases with expression of mdm2 in one of them. Overall, p53 deletion and/or overexpression of mdm2 was found in 71% of cases. Ten of 19 patients had a blastoid MCL, including all 5 patients who were Ki67 positive, 6 of the 7 patients expressing mdm2 and one of the 2 patients expressing p53. There was no correlation between p53 deletion and morphologic subtypes. All patients with blastoid MCL have died after a median time of 25 months. INTERPRETATION AND CONCLUSIONS: In MCL in leukemic phase there is a high frequency of p53 deletion and/or overexpression of mdm2. In contrast, over expression of p53 is relatively rare. Overexpression of mdm2 is seen predominantly in blastoid MCL, the latter being characterized by a short median survival, and seems unrelated to a numerical gain of chromosome 12. It does not reflect a high proliferative rate but might indicate an alternative mechanism of inactivating p53 in prognostically adverse types of MCL.
BACKGROUND AND OBJECTIVES: In mantle cell lymphoma (MCL), abnormalities additional to t(11;14) including those affecting genes involved in the p53 pathway, are important for disease development and progression. This study aimed to assess the frequency, relationship and impact of p53 abnormalities and those of its inhibitor mdm2 in blastoid and non-blastoid MCL in leukemic phase. DESIGN AND METHODS: Isolated blood lymphocytes from 21 patients with MCL in leukemic phase, characterized by the presence of t(11;14), were analyzed by flow cytometry and by fluorescent in situ hybridization in order to investigate whether there is a correlation between overexpression and deletion of p53, overexpression of mdm2 and gain of chromosome 12. Results were also correlated with morphologic subtypes, proliferative activity assessed by expression of Ki67 and clinical outcome. RESULTS: Cells from 2/21 (10%) and 7/21 (33%) patients overexpressed p53 and mdm2, respectively. No single case expressed both proteins. Ten out of 19 (53%) patients had a hemizygous loss of 17p (p53) including the 2 patients (11%) overexpressing p53. Gains of chromosome 12 (mdm2) were found in only 2 cases with expression of mdm2 in one of them. Overall, p53 deletion and/or overexpression of mdm2 was found in 71% of cases. Ten of 19 patients had a blastoid MCL, including all 5 patients who were Ki67 positive, 6 of the 7 patients expressing mdm2 and one of the 2 patients expressing p53. There was no correlation between p53 deletion and morphologic subtypes. All patients with blastoid MCL have died after a median time of 25 months. INTERPRETATION AND CONCLUSIONS: In MCL in leukemic phase there is a high frequency of p53 deletion and/or overexpression of mdm2. In contrast, over expression of p53 is relatively rare. Overexpression of mdm2 is seen predominantly in blastoid MCL, the latter being characterized by a short median survival, and seems unrelated to a numerical gain of chromosome 12. It does not reflect a high proliferative rate but might indicate an alternative mechanism of inactivating p53 in prognostically adverse types of MCL.
Authors: Kebria Hezaveh; Andreas Kloetgen; Stephan H Bernhart; Kunal Das Mahapatra; Dido Lenze; Julia Richter; Andrea Haake; Anke K Bergmann; Benedikt Brors; Birgit Burkhardt; Alexander Claviez; Hans G Drexler; Roland Eils; Siegfried Haas; Steve Hoffmann; Dennis Karsch; Wolfram Klapper; Kortine Kleinheinz; Jan Korbel; Helene Kretzmer; Markus Kreuz; Ralf Küppers; Chris Lawerenz; Ellen Leich; Markus Loeffler; Luisa Mantovani-Loeffler; Cristina López; Alice C McHardy; Peter Möller; Marius Rohde; Philip Rosenstiel; Andreas Rosenwald; Markus Schilhabel; Matthias Schlesner; Ingrid Scholz; Peter F Stadler; Stephan Stilgenbauer; Stéphanie Sungalee; Monika Szczepanowski; Lorenz Trümper; Marc A Weniger; Reiner Siebert; Arndt Borkhardt; Michael Hummel; Jessica I Hoell Journal: Haematologica Date: 2016-07-06 Impact factor: 9.941
Authors: Julia Slotta-Huspenina; Ina Koch; Laurence de Leval; Gisela Keller; Margit Klier; Karin Bink; Marcus Kremer; Mark Raffeld; Falko Fend; Leticia Quintanilla-Martinez Journal: Haematologica Date: 2012-02-07 Impact factor: 9.941
Authors: Irene M Ghobrial; Daniel J McCormick; Scott H Kaufmann; Alexey A Leontovich; David A Loegering; Nga T Dai; Kelly L Krajnik; Mary J Stenson; Mona F Melhem; Anne J Novak; Stephen M Ansell; Thomas E Witzig Journal: Blood Date: 2005-01-13 Impact factor: 22.113
Authors: Richard J Jones; Veerabhadran Baladandayuthapani; Sattva Neelapu; Luis E Fayad; Jorge E Romaguera; Michael Wang; Rakesh Sharma; Dajun Yang; Robert Z Orlowski Journal: Blood Date: 2011-08-15 Impact factor: 22.113
Authors: Heike Stöcklein; Grit Hutter; Jörg Kalla; Elena Hartmann; Yvonne Zimmermann; Tiemo Katzenberger; Patrick Adam; Ellen Leich; Sylvia Höller; Hans Konrad Müller-Hermelink; Andreas Rosenwald; German Ott; Martin Dreyling Journal: J Hematop Date: 2008-07-05 Impact factor: 0.196
Authors: Zijun Y Xu-Monette; Michael B Møller; Alexander Tzankov; Santiago Montes-Moreno; Wenwei Hu; Ganiraju C Manyam; Louise Kristensen; Lei Fan; Carlo Visco; Karen Dybkaer; April Chiu; Wayne Tam; Youli Zu; Govind Bhagat; Kristy L Richards; Eric D Hsi; William W L Choi; J Han van Krieken; Qin Huang; Jooryung Huh; Weiyun Ai; Maurilio Ponzoni; Andrés J M Ferreri; Lin Wu; Xiaoying Zhao; Carlos E Bueso-Ramos; Sa A Wang; Ronald S Go; Yong Li; Jane N Winter; Miguel A Piris; L Jeffrey Medeiros; Ken H Young Journal: Blood Date: 2013-08-27 Impact factor: 22.113
Authors: Stefania Trino; Luciana De Luca; Ilaria Laurenzana; Antonella Caivano; Luigi Del Vecchio; Giovanni Martinelli; Pellegrino Musto Journal: Front Pharmacol Date: 2016-12-16 Impact factor: 5.810
Authors: Joana M Rodrigues; May Hassan; Catja Freiburghaus; Christian W Eskelund; Christian Geisler; Riikka Räty; Arne Kolstad; Christer Sundström; Ingrid Glimelius; Kirsten Grønbaek; Anna Kwiecinska; Anna Porwit; Mats Jerkeman; Sara Ek Journal: Br J Haematol Date: 2020-08-04 Impact factor: 8.615